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Biomedical subjects

M S Simberkoff

Publications and source records attributed to M S Simberkoff.

At least 55 records · Page 3Linked to original sources

High-dose corticosteroids as adjunct therapy in severe Pneumocystis carinii pneumonia.

Three patients with severe Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome, not responding to specific therapy with trimethoprim/sulfamethoxazole, were treated with a 24-hour course of high-dose methylprednisolone. Rapid improvements in the clinical status and the chest X-rays were detected. In two of the patients, in whom lung biopsy was performed before initiation of corticosteroids, an intense interstitial mononuclear cell infiltrate was seen. In the one patient who had lung biopsy after corticosteroid therapy, a scanty amount of mononuclear cells was demonstrated in the interstitium. Our experience suggests that corticosteroids may be useful as adjunctive agents in the treatment of severe P. carinii pneumonia not responding to specific anti-Pneumocystis therapy. This may be a result of inhibition of mononuclear cell accumulation within the lung by the steroid therapy.

Acquired Immunodeficiency Syndrome↗

Antibiotic-resistant isolates of Streptococcus pneumoniae from clinical specimens: a cluster of serotype 19A organisms in Brooklyn, New York.

Ten of 294 isolates of Streptococcus pneumoniae from patients enrolled in a Veterans Administration Cooperative Studies Program trial of pneumococcal vaccine efficacy were moderately resistant or resistant to penicillin. Nine of these organisms were serotype 19A isolated from patients at the Brooklyn (New York) V.A. Medical Center over an 18-month period (March 1983-November 1984). The minimal inhibitory concentration of penicillin for these pneumococci ranged from 1.0 to 2.0 micrograms/ml by the agar dilution technique and from 4.0 to 8.0 micrograms/ml by tube dilution. These organisms were resistant also to other beta-lactam antibiotics and to tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. They were sensitive to erythromycin, clindamycin, vancomycin, and rifampin. The epidemiological source of these isolates was not discovered. However, it is possible that a focus of multiple antibiotic-resistant serotype 19A S. pneumoniae is present in Brooklyn.

Drug Resistance, Microbial↗

Comparative bactericidal activity of penicillin-netilmicin and penicillin-gentamicin against enterococci.

The synergistic bactericidal activity of netilmicin in combination with penicillins was compared with that of gentamicin and streptomycin against 16 clinical isolates of enterococci. In a macrodilution chessboard assay against multiple combinations of penicillin, gentamicin and netilmicin, bactericidal activity uniformly occurred at two- to four-fold lower concentrations of penicillin + netilmicin than with penicillin + gentamicin. With four strains, penicillin + netilmicin produced up to ten-fold greater killing than penicillin + gentamicin after 6 h of incubation. With one strain, 3 X log10 greater killing occurred with netilmicin after 24 h. Netilmicin was two- to four-fold more active than gentamicin when combined with penicillinase-resistant penicillins. The bactericidal activity of netilmicin against enterococci is equal to or greater than that of gentamicin, either alone or when combined with penicillins.

Drug Synergism↗

Bactericidal activity of ciprofloxacin against amikacin- and cefotaxime-resistant gram-negative bacilli and methicillin-resistant staphylococci.

The MICs and MBCs of ciprofloxacin were determined for clinical isolates of antibiotic-resistant aerobic bacteria. Decreased susceptibility to ciprofloxacin of cefotaxime- and amikacin-resistant Serratia marcescens and amikacin-resistant Pseudomonas aeruginosa strains were noted. The data suggest that ciprofloxacin susceptibility should be carefully monitored in treating patients with hospital-acquired bacterial infections.

Amikacin↗

Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Diagnostic features and outcome of treatment.

Between 1 January 1981 and 1 December 1984, 34 of 396 patients with the acquired immunodeficiency syndrome (AIDS) developed cryptococcal infections. Twenty-six cases are reviewed. Twenty-two patients had brain or meningeal disease; the others had pulmonary disease (2 patients), pericarditis (1 patient), and antigenemia (1 patient). During treatment, 3 patients died of cryptococcosis and 3 died of other causes. Fifteen patients were followed for more than 6 weeks after treatment. Of 8 patients who received no additional amphotericin B, 4 had relapses and died of cryptococcosis within 6 months, 3 died of other causes, and 1 survived. Of 7 patients who received maintenance therapy with amphotericin B, none had relapses, 3 died of other causes, and 4 survived. Our data suggest that maintenance therapy with amphotericin may be needed to prevent relapse in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Amikacin-resistant gram-negative bacilli: correlation of occurrence with amikacin use.

The incidence of amikacin resistance among gram-negative bacilli isolated at the New York V.A. Medical Center increased from 2.0% to greater than 7% during an 18-month period from January 1980 to July 1981. This increase coincided with a threefold increase in amikacin use at this institution. The amikacin-resistant (AKR) isolates most frequently recovered in 1981 were species of Klebsiella, Serratia, and Pseudomonas. These organisms were recovered from multiple sites, including urine, sputum, wounds, blood, peritoneal fluid, and pleural fluid. The amikacin-modifying enzyme 6'-N-acetyltransferase was detected in 27 (67.5%) of 40 randomly selected AKR isolates. These data indicate that resistance to amikacin in this hospital is enzymatically mediated in most strains of AKR Klebsiella and Serratia and in about one-third of AKR strains of P. aeruginosa. This finding supports the conclusion that amikacin resistance is enhanced by the pressure of increased amikacin use.

Acetyltransferases↗

Clinical efficacy of a synergistic combination of cefotaxime and amikacin against multiresistant Pseudomonas and Serratia infections.

The synergistic activity of cefotaxime and amikacin against 21 highly resistant Pseudomonas aeruginosa and Serratia marcescens isolates was evaluated in-vitro by the checkerboard tube dilution method and in-vivo in five patients with serious infections caused by these organisms. All isolates were resistant to gentamicin, tobramycin, amikacin, and cefotaxime. Synergy was observed in 90% of isolates and occurred when the MIC of amikacin was less than 256 mg/l and of cefotaxime less than 1024 mg/l. A clinical response occurred in 100% and bacteriological cure in 80% of patients. Our results demonstrate a high degree of synergism between amikacin and cefotaxime in-vitro and clinical efficacy in the treatment of infections due to multiply-resistant Pseudomonas and Serratia species.

Aged↗

Prospective evaluation of moxalactam therapy for gram-negative bacillary meningitis.

In a prospective evaluation twenty patients with gram-negative bacillary meningitis were treated with moxalactam, either alone or in conjunction with other antibiotics. Of thirteen patients who received only moxalactam, eight recovered, one failed to respond, and five died of causes other than meningitis. Cultures of CSF were negative before death in each instance. Thirteen (65%) of 20 treated patients recovered. Reversible hypoprothrombinemia and bleeding occurred secondary to moxalactam therapy in one patient. The mortality from gram-negative bacillary meningitis remains high owing to the incidence of associated underlying disease. Moxalactam brings about bacteriologic control in a large proportion of patients who are infected with highly sensitive gram-negative enteric bacilli.

Acinetobacter Infections↗

Streptococcus pneumoniae infections and bacteremia in patients with acquired immune deficiency syndrome, with report of a pneumococcal vaccine failure.

Five patients had Streptococcus pneumoniae infections among the 35 hospitalized with acquired immune deficiency syndrome (AIDS) at the New York Veterans Administration Medical Center between January 1, 1982, and June 30, 1983. Three of these patients had pneumococcal bacteremia and 2 had pneumonia without bacteremia. Twenty-seven bacteremic S. pneumoniae infections occurred among 5,143 patients without AIDS admitted to the Medical Service of this hospital during the same period. Thus, pneumococcal bacteremia was more likely to occur in patients with AIDS than in the general hospitalized population (x2 = 26, p = less than 0.001). Two of the bacteremic infections were caused by S. pneumoniae type 4. One of these occurred in a patient who had been inoculated with the 14 valent pneumococcal vaccine 5 months earlier. There were no significant differences in concentrations of radioimmunoassay antibody to type 4 pneumococcal polysaccharide in sequential serum samples collected from this patient, and opsonic titers to this organism were not detected. It is concluded that pneumococcal infections are very common among patients with AIDS, and may not be prevented by active immunoprophylaxis.

Acquired Immunodeficiency Syndrome↗

Ceftazidime therapy of infections caused by Enterobacteriaceae and Pseudomonas aeruginosa.

Sixteen patients with serious Gram-negative bacillary infections were treated with intravenous ceftazidime, 2 g every 8 h. The majority of patients had bacteraemia or pneumonitis or both. Ten patients were cured and six improved. Seven of ten patients infected with Pseudomonas aeruginosa were cured, and three improved. No adverse reactions occurred. Four strains of Ps. aeruginosa became resistant to ceftazidime in patients who were cured or improved clinically. Ceftazidime is effective as single drug therapy for serious Gram-negative infections, including those due to Ps. aeruginosa.

Adult↗

Radioimmunoassay and opsonic antibody responses to pneumococcal capsular polysaccharide vaccine in serum and ascitic fluid of cirrhotic patients.

Pneumococcal capsular polysaccharide vaccine was administered to 19 cirrhotic patients and to 25 control subjects. Radioimmunoassay antibody concentration and opsonic titers (OT) were measured in sera and ascites collected before and 3 to 4 weeks after inoculation. The geometric mean antibody concentrations in prevaccination sera from the cirrhotic patients were significantly increased to types 3, 4, 7F, 8, 9N, and 12F antigens, and in postinoculation sera their geometric mean antibody concentration was increased to types 3, 9N, and 12F antigens. OT to Streptococcus pneumoniae type 3 correlated with the radioimmunoassay antibody concentration in postinoculation sera. Of 14 cirrhotic subjects, 3 had OT of greater than or equal to 4 in prevaccination sera, and the highest OT and radioimmunoassay antibody concentration were observed in postinoculation specimens from this group. Antibody and OT against S. pneumoniae type 3 were also observed in ascitic specimens. These data suggest that cirrhotic subjects respond to pneumococcal capsular polysaccharide with antibodies in both serum and ascitic fluid. However, the protective efficacy of this antibody response must be assessed by larger prospective studies.

Antibodies, Bacterial↗

Efficacy of a twelve-hourly ceftriaxone regimen in the treatment of serious bacterial infections.

Eighteen patients with 21 serious infections were treated with ceftriaxone, 1 g intravenously every 12 h, for a mean duration of 8 days. Eighteen gram-negative and two gram-positive organisms were isolated. Sites of infection included blood (three patients), urinary tract (six patients), respiratory tract (seven patients), biliary tract (three patients), ascitic fluid (one patient), and skin (one patient). Serum, bile, and ascitic fluid concentrations of ceftriaxone were in excess of the minimal bactericidal concentration required for the infecting organism in all cases. A bacteriological response was demonstrated in 94% of the infections. A clinical response occurred in four infections from which no pathogens were recovered. In one patient, ceftriaxone failed to eradicate a peritoneal infection due to Bacteroides fragilis. In two patients, superinfection with enterococci developed both during and after therapy. Systemic tolerance to ceftriaxone was excellent.

Aged↗

Pharmacokinetic characteristics of intravenous ceftriaxone in normal adults.

The multiple-dose pharmacokinetics and tolerance of intravenous ceftriaxone were investigated in 44 adults with normal renal function. Doses of 0.5, 1.0, and 2.0 g every 12 h and 2 g every 24 h were administered intravenously at a constant rate over 30 min. Plasma and urine samples were collected after the first (day 1) and last (day 4) dose and assayed for ceftriaxone by high-pressure liquid chromatography. Considering all four doses, mean peak plasma concentrations ranged from 79 to 255 micrograms/ml on day 1 and from 101 to 280 micrograms/ml on day 4. Trough concentrations at 12 h on day 1 were 15 to 45 micrograms/ml and 20 to 59 micrograms/ml on day 4. After a dose regimen of 2 g every 24 h, trough levels were still in the clinically therapeutic range (13 to 15 microgram/ml). The mean beta-phase t1/2 was markedly long (6.3 to 6.9 h) and was independent of dose. The fraction of dose excreted unchanged in the urine (0.33 to 0.44) indicated a substantial nonrenal mechanism of elimination. The plasma clearance ranged between 1,002 and 1,449 ml/h, and renal clearance ranged from 353 to 529 ml/h. The apparent volume of distribution varied from 9.2 to 13.5 liters. The dose-related increases in calculated Vd and Clp could be attributed to concentration-dependent plasma protein binding because of a larger free fraction of drug at higher concentrations. The drug was well tolerated, and no significant clinical or laboratory abnormalities were noted.

Adult↗

Host defense and antimicrobial therapy in adult gram-negative bacillary meningitis.

Effective therapy for aerobic gram-negative bacillary meningitis is limited by antibiotic resistance among many pathogens and by poor diffusion of some antibiotics into the subarachnoid space. The host response to suppurative meningitis caused by all encapsulated bacteria is impaired by a deficiency of complement and opsonic activity in infected spinal fluid; consequently, therapy with bactericidal antibiotics is preferred. Chloramphenicol diffuses well into cerebrospinal fluid, but is bacteristatic against enteric gram-negative bacilli. Although aminoglycosides are bactericidal, their use requires daily intralumbar or intraventricular injections. Newer cephalosporin compounds, moxalactam and cefotaxime, are bactericidal at very low concentrations and diffuse well from serum to infected spinal fluid. Clinical trials with moxalactam suggest that it is the most effective regimen for enteric gram-negative bacillary meningitis in adults; Pseudomonas aeruginosa and acinetobacter meningitis are most susceptible to a combination of intravenous ticarcillin and aminoglycoside, plus intrathecal aminoglycoside.

Adult↗

Mycobacterium avium-intracellulare: a cause of disseminated life-threatening infection in homosexuals and drug abusers.

Five men developed disseminated infection with Mycobacterium avium-intracellulare. These patients all lived in the New York City area and presented with their illnesses between January 1981 and September 1981; four were homosexual and one was an intravenous drug abuser. Four patients died. All five patients had defects in the cell-mediated immune response. The infections were characterized histopathologically by poor or absent granulomatous tissue reaction. Clinical isolates of M. avium-intracellulare from all five patients agglutinated commonly used antimycobacterial drugs. The spectrum of opportunistic infections among populations of homosexuals and drug abusers should be expanded to include disseminated disease due to M. avium-intracellulare.

Adult↗

Immunogenic effect of inactivated hepatitis B vaccine: comparison of 20 microgram and 40 microgram doses.

The immunogenic effect of inactivated hepatitis B vaccine (Merck Heptavax B) was evaluated in 202 seronegative healthy medical personnel. Three inoculations of vaccine were given at 1-month intervals. Of 116 vaccinees who received a 40-microgram dose, 39% had an anti-HBs response 1 month after the first dose, 88% 1 month after the second dose, and 99% 1 month after the third dose. Of 86 vaccinees who received a 20 microgram dose, 40% had an anti-HBs response 1 month after the first dose, 79% after the second dose, and 95% after the third dose. These results confirm the high immunogenic effect of a 20-microgram dose of vaccine.

Adult↗